Observations on the host response to some helminth infections

Immunological aspects of the host-parasite relationship were investigated in two systems: Nippostrongylus brasiliensis in the rat and Haemonchus contortus in sheep and are described in Sections I and II of this thesis respectively. The objective of the work described in Section I was to study the uptake of labelled metabolites by the parasites under a variety of different circumstances to test the validity of such measurements as an index of immunological worm damage. This largely successful in that in all the circumstances examined, worm expulsion was proceeded by a marked depression in their metabolite uptake. However the converse was not always true, i.e. a depressed metabolite uptake was not necessarily followed by expulsion. For instance in both neonatally infected rats, in rats treated with Depoprovera (a long acting progesterone) and also in female rats in pro-oestrus, worm expulsion was significantly delayed although metabolic damage evidently occurred at the normal time. This finding is important since it implies that immunologically damaged worms are still able to persist in the host and that a further, possibly non-immunological mechanism, is needed to bring about their subsequent physical expulsion. One of the most interesting features of this section was the observation of significant 'strain' differences in the immune response of the host to N. brasiliensis, i.e. the Aberdeen strain of rat appeared to selfcure earlier than the London strain. An opportunity arose to pursue this line of research in relation to an economically important helminth disease in East Africa namely H. contortus in sheep. The experiments described in Section II of the thesis demonstrate that in Merino sheep in East Africa there are significant strain differences in susceptibility to I-L contortus and that these strain differences are linked to haemoglobin type. It was shown that sheep of haemoglobin type A are more resistant than those with haemoglobin B and that AB animals occupy an intermediate position. These differences were demonstrated by parasitological, haematological and pathophysiological measurements- However this strain difference is not absolute and appeared to be dependent on the size of the challenge infection. At certain levels of infection the strain difference in susceptibility tended to disappear. It has been shown that haemoglobin B gene is predominant in Kenya, although the incidence of the A gene tends to increase in the wetter areas. One possible reason for this gradient of haemoglobin genes could be related to the higher incidence of H. contortus in wetter areas which might favour the selection of the A gene which confers more resistance to H. contortus. The practical application of this strain difference in resistance to haemonchosis is discussed